Erythromycins A through D, represented by formula (E),
______________________________________ 1 #STR2## Erythromycin R.sup.a R.sup.b ______________________________________ A --OH --CH.sub.3 B --H --CH.sub.3 C --OH --H D --H --H ______________________________________
are well-known and potent antibacterial agents, used widely to treat and prevent bacterial infection. As with other antibacterial agents, however, bacterial strains having resistance or insufficient susceptibility to erythromycin have been identified. Also, erythromycin A has only weak activity against Gram-negative bacteria. Therefore, there is a continuing need to identify new erythromycin derivative compounds which possess improved antibacterial activity, which have less potential for developing resistance, which possess the desired Gram-negative activity, or which possess unexpected selectivity against target microorganisms. Consequently, numerous investigators have prepared chemical derivatives of erythromycin in an attempt to obtain analogs having modified or improved profiles of antibiotic activity.
We have discovered that multicyclic erythromycin derivatives containing one or more fused aryl or heteroaryl ring possess significant activity against selected microorganisms.
Other variously modified erythromycin compounds are known, but none possess the fused aryl or heteroaryl ring moieties of the present invention (see, for example, Agouridas et al., European application EP676409, published Oct. 11, 1995; Agouridas et al., U.S. Pat. No. 5,527,780, issued Jun. 18, 1996; Agouridas et al., U.S. Pat. No. 5,543,400, issued Aug. 6, 1996; Kashimura et al., U.S. Pat. No. 5,403,923, issued Apr. 4, 1995, and Asaka et al., PCT application WO 93/21200, published Oct. 28, 1993). Also, Agouridas et al., U.S. Pat. No. 5,561,118, issued Oct. 1, 1996, describe erythromycin derivatives with the 3-cladinose moiety removed.